The project is designed to determine if cannabis sativa derivatives do indeed induce brain damage and if they do, what is the hazardous dose level and exposure period? Two methods are being used to answer questions with respect to dose levels (relevant to man): (1) a smoking procedure permitting simulation of man's smoking pattern, and (2) radioimmune assay for accurate determination of plasma levels of various cannabis ingredients. To establish a complete dose response curve, data will be gathered from smoking rhesus monkeys (some with implanted deep electrodes and some intact) with respect to relevance of dose per exposure and total dose effect. Acute and chronic effects on brain function of certain cannabis derivatives and metabolites will also be determined by intravenous injection of the compounds into monkeys prepared with deep electrodes. Light and electron microscopic studies will be performed on the brains of all experimental monkeys in follow-up to the physiologic studies. BIBLIOGRAPHIC REFERENCES: Heath, R.G. "Marihuana and delta 9-Tetrahydrocannabinol: Acute and chronic effects on brain function of monkeys," in Pharmacology of Marihuana, ed. by Braude, M.C., and Szaram, S. Volume 1 - Monograph of the National Institute on Drug Abuse. New York, Raven Press, 1976, pp. 345-356. Heath, R.G. "Cannabis Sativa Derivatives: Effects on Brain Function of Monkeys," in Marihuana: Chemistry, Biochemistry, and Cellular Effects, ed. by Nahas, G.G. Springer-Verlag New York Inc., 1976, pp. 507-519.